Mitochondrial haplotype modulates genome expression and mitochondrial structure/function in cardiomyocytes following volume overload.

Mitochondrial DNA (mtDNA) haplotype regulates mitochondrial structure/function and reactive oxygen species in aortocaval fistula (ACF) in mice. Here, we unravel the mitochondrial haplotype effects on cardiomyocyte mitochondrial ultrastructure and transcriptome response to ACF in vivo. Phenotypic responses and quantitative transmission electron microscopy (TEM) and RNA sequence at 3 days were determined after sham surgery or ACF in vivo in cardiomyocytes from wild-type (WT) C57BL/6J (C57:C57) and C3H/HeN (C3H:C3H) and mitochondrial nuclear exchange mice (C57:C3H or C3H:C57).

A Procedural Guide for Implanting the Cordella Pulmonary Artery Pressure Sensor.

The Cordella pulmonary artery (PA) pressure sensor (Endotronix, Inc) is an investigational, wireless, microelectromechanical system (MEMS) sensor that allows remote monitoring of PA pressures. Understanding the implantation procedure and technical nuances is key to safe, efficient, and effective implantation to allow for successful use of the PA pressure sensor over the long term. We provide a summary of the implantation procedure and present a series of cases detailing the Cordella PA pressure sensor implantation in the United States and Europe.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

Background: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management.

Methods: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms.

The GUIDE-HF trial of pulmonary artery pressure monitoring in heart failure: impact of the COVID-19 pandemic.

Aims: During the coronavirus disease 2019 (COVID-19) pandemic, important changes in heart failure (HF) event rates have been widely reported, but few data address potential causes for these changes; several possibilities were examined in the GUIDE-HF study.

Methods And Results: From 15 March 2018 to 20 December 2019, patients were randomized to haemodynamic-guided management (treatment) vs. control for 12 months, with a primary endpoint of all-cause mortality plus HF events.

Concurrent Assessment of the CardioMEMS HF System and HeartLogic HF Diagnostic: A Retrospective Case Series.

Background: Heart failure (HF) causes high morbidity and mortality despite advances in medical therapy. Remote patient monitoring for HF allows for the optimization of medical therapy and prevention of HF hospitalizations. This study is the first to assess pulmonary artery diastolic pressures (PADP) using the CardioMEMS HF System (CMEMS) and cardiac implantable electronic device-based multisensor indexes (HeartLogic index [HLI]) using the HeartLogic HF Diagnostic (HL) in a small, retrospective cohort of patients with HF at a single center.

Development and implementation of a remote patient monitoring program for heart failure: a single-centre experience.

Aims: Remote patient monitoring (RPM) in the management of heart failure (HF), including telemonitoring, thoracic impedance, implantable pulmonary artery pressure (PAP) monitors, and cardiac implantable electronic device (CIED)-based sensors, has had varying outcomes in single platform studies. Uncertainty remains regarding the development of single-centre RPM programs; additionally, no studies examine the effectiveness of dual platform RPM programs for HF. This study describes the implementation and outcomes of a dual platform RPM program for HF at a single centre.

Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure.

Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later.

Catheter-directed treatment for acute pulmonary embolism: Systematic review and single-arm meta-analyses.

Background: We sought to estimate the efficacy and safety outcomes of catheter-directed treatment (CDT) for patients with acute pulmonary embolism (PE).

Methods: We searched SCOPUS for studies reporting outcomes after CDT for acute PE. Studies were categorized in three groups for analyses due to heterogeneity in the classification of acute PE: 1) patients with PE causing right ventricular dysfunction and haemodynamic instability: unstable haemodynamic status, 2) patients with PE causing right ventricular dysfunction where study outcomes were not stratified by haemodynamic status: stable and unstable haemodynamic status, and 3) patients with PE causing right ventricular dysfunction who remained haemodynamically stable: stable haemodynamic status.

Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function.

Objective: Recent studies have demonstrated improved outcomes in patients receiving early surgery for degenerative mitral regurgitation (MR) rather than adhering to conventional guidelines for surgical intervention. However, studies providing a mechanistic basis for these findings are limited.

Methods: Left ventricular (LV) myocardium from 22 patients undergoing mitral valve repair for American Heart Association class I indications was evaluated for desmin, the voltage-dependent anion channel, α-B-crystallin, and α, β-unsaturated aldehyde 4-hydroxynonenal by fluorescence microscopy.

Cardiomyocyte mitochondrial oxidative stress and cytoskeletal breakdown in the heart with a primary volume overload.

Left ventricular (LV) volume overload (VO) results in cardiomyocyte oxidative stress and mitochondrial dysfunction. Because mitochondria are both a source and target of ROS, we hypothesized that the mitochondrially targeted antioxidant mitoubiquinone (MitoQ) will improve cardiomyocyte damage and LV dysfunction in VO. Isolated cardiomyocytes from Sprague-Dawley rats were exposed to stretch in vitro and VO of aortocaval fistula (ACF) in vivo.

Whole-genome profiling highlights the molecular complexity underlying eccentric cardiac hypertrophy.

Objectives: Heart failure is typically preceded by myocardial hypertrophy and remodeling, which can be concentric due to pressure overload (PO), or eccentric because of volume overload (VO). The molecular mechanisms that underlie these differing patterns of hypertrophy are distinct and have yet to be fully elucidated. Thus, the goal of this work is to identify novel therapeutic targets for cardiovascular conditions marked by hypertrophy that have previously been resistant to medical treatment, such as a pure VO.

Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic function in cardiac volume overload.

Xanthine oxidase (XO) is increased in human and rat left ventricular (LV) myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease mitochondrial respiration and contractile function. Thus, we tested the hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV function in chronic ACF in the rat.

Aldosterone receptor antagonists: current perspectives and therapies.

Aldosterone is a downstream effector of angiotensin II in the renin-angiotensin-aldosterone system and binds to the mineralocorticoid receptor. The classical view of aldosterone primarily acting at the level of the kidneys to regulate plasma potassium and intravascular volume status is being supplemented by evidence of new "off-target" effects of aldosterone in other organ systems. The genomic effects of aldosterone are well known, but there is also evidence for non-genomic effects and these recently identified effects of aldosterone have required a revision in the traditional view of aldosterone's role in human health and disease.

Recent advancements in the treatment of resistant hypertension.

The 2008 scientific statement from the American Heart Association defined resistant hypertension as blood pressure remaining above goal (< 140/90 mm Hg for the general population and < 130/80 mm Hg for patients with diabetes or renal disease) despite the concurrent use of optimal doses of 3 antihypertensive agents of different classes, ideally including a diuretic. Since then, there has been increasing recognition and characterization of patients with resistant hypertension and development of treatment strategies to treat this high-risk population. The role of aldosterone in resistant hypertension has gained increasing recognition.

Effect of warfarin on outcomes in septuagenarian patients with atrial fibrillation.

Anticoagulation has been shown to decrease ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who constitute most patients with AF. Of the 4,060 patients (mean age 65 years, range 49 to 80) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2,248 (55% of 4,060) were 70 to 80 years of age, 1,901 of whom were receiving warfarin.

Bucindolol, systolic blood pressure, and outcomes in systolic heart failure: a prespecified post hoc analysis of BEST.

Background: In the Beta-Blocker Evaluation of Survival Trial (BEST), systolic blood pressure (SBP) ≤ 120 mm Hg was an independent predictor of poor prognosis in ambulatory patients with chronic systolic heart failure (HF). Because SBP is an important predictor of response to β-blocker therapy, the BEST protocol prespecified a post hoc analysis to determine whether the effect of bucindolol varied by baseline SBP.

Methods: In the BEST, 2706 patients with chronic systolic (left ventricular ejection fraction < 35%) HF and New York Heart Association class III (92%) or IV (8%) symptoms and receiving standard background therapy were randomized to receive either bucindolol (n = 1354) or placebo (n = 1354).

Isolated diastolic hypotension and incident heart failure in older adults.

Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure.

Association between smoking and outcomes in older adults with atrial fibrillation.

Tobacco smoking is a risk factor for atrial fibrillation (AF), but little is known about the impact of smoking in patients with AF. Of the 4060 patients with recurrent AF in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 496 (12%) reported having smoked during the past two years. Propensity scores for smoking were estimated for each of the 4060 patients using a multivariable logistic regression model and were used to assemble a matched cohort of 487 pairs of smokers and nonsmokers, who were balanced on 46 baseline characteristics.

Reduced right ventricular ejection fraction and increased mortality in chronic systolic heart failure patients receiving β-blockers: insights from the BEST trial.

Background: Right ventricular ejection fraction (RVEF) < 20% is an independent predictor of poor outcomes in patients with advanced chronic systolic heart failure (HF). The aim of this study was to examine if the adverse effect of abnormally reduced RVEF varies by the receipt of beta-blockers.

Methods: In the Beta-Blocker Evaluation of Survival Trial (BEST), 2708 patients with chronic advanced HF and left ventricular ejection fraction < 35%, receiving standard background therapy with renin-angiotensin inhibition, digoxin, and diuretics, were randomized to receive bucindolol or placebo.

Relation of baseline systolic blood pressure and long-term outcomes in ambulatory patients with chronic mild to moderate heart failure.

We studied the impact of baseline systolic blood pressure (SBP) on outcomes in patients with mild to moderate chronic systolic and diastolic heart failure (HF) in the Digitalis Investigation Group trial using a propensity-matched design. Of 7,788 patients, 7,785 had baseline SBP data and 3,538 had SBP ≤ 120 mm Hg. Propensity scores for SBP ≤ 120 mm Hg, calculated for each of the 7,785 patients, were used to assemble a matched cohort of 3,738 patients with SBP ≤ 120 and >120 mm Hg who were well-balanced in 32 baseline characteristics.

Rheumatic heart disease and risk of incident heart failure among community-dwelling older adults: a prospective cohort study.

Background: Little is known about the association of rheumatic heart disease (RHD) with incident heart failure (HF) among older adults.

Design: Cardiovascular Health Study, a prospective cohort study.

Methods: Of the 4,751 community-dwelling adults ≥ 65 years, free of prevalent HF at baseline, 140 had RHD, defined as self-reported physician-diagnosed RHD along with echocardiographic evidence of left-sided valvular disease.

O(2)-sensing signal cascade: clamping of O(2) respiration, reduced ATP utilization, and inducible fumarate respiration.

These studies explore the consequences of activating the prolyl hydroxylase (PHD) O(2)-sensing pathway in spontaneously twitching neonatal cardiomyocytes. Full activation of the PHD pathway was achieved using the broad-spectrum PHD inhibitor (PHI) dimethyloxaloylglycine (DMOG). PHI treatment of cardiomyocytes caused an 85% decrease in O(2) consumption and a 300% increase in lactic acid production under basal conditions.

The prolyl hydroxylase oxygen-sensing pathway is cytoprotective and allows maintenance of mitochondrial membrane potential during metabolic inhibition.

The cellular oxygen sensor is a family of oxygen-dependent proline hydroxylase domain (PHD)-containing enzymes, whose reduction of activity initiate a hypoxic signal cascade. In these studies, prolyl hydroxylase inhibitors (PHIs) were used to activate the PHD-signaling pathway in cardiomyocytes. PHI-pretreatment led to the accumulation of glycogen and an increased maintenance of ATP levels in glucose-free medium containing cyanide.